Lactoperoxidase (LP), hydrogen peroxide (H2O2) and thiocyanate ion (SCN-) form a bacteriostatic system in human saliva. The oral "lactic-acid bacteria" release H2O2 as a by-product of carbohydrate metabolism. LP catalyzes the oxidation of SCN- by H2O2 to yield hypothiocyanite ion (OSCN-), which is in acid-base equilibrium with hypothiocyanous acid (HOSCN). HOSCN oxidizes essential sulfhydryl groups of bacterial enzymes and transport systems, resulting in inhibition of metabolism and growth. Certain bacteria such as S. mutans have a limited resistance to inhibition, due to their ability to rapidly reduce certain disulfide compounds to the sulfhydryl forms. These low-mol. wt. sulfhydryl compounds protect essential protein sulfhydryls by reacting with the inhibitor and reducing it back to SCN-. These studies will evaluate agents that may increase LP antimicrobial action in saliva: (1) by increasing the peroxide supply so as to overcome the limited resistance to inhibition, (2) by increasing the stability and/or reactivity of the inhibitor, and (3) by interfering with the activities responsible for resistance. The more promising agents will be studied with S. mutans, other oral streptococci, and streptococci that do not colonize the mouth as target microorganisms. Agents to be tested include amino sugars as substrates that result in increased H2O2 production, H2O2 and alkyl peroxides, glucose oxidase, plumbagan, iodide, sulfonamide compounds, cyanide, and inhibitors or competitive substrates of the activities involved in resistance. These studies will provide information about the interaction of the LP system with the bacteria that can survive and grow in the presence of this antimicrobial system. The studies should also provide a basis for evaluating the significance of the LP system in natural resistance to oral disease, (1) by developing methods to measure LP antimicrobial activity that could be used in the clinical environment, and (2) by identifying agents that can increase the efficacy or selectivity of antimicrobial action against oral pathogens. Such agents could then be used to compare the effect of the LP system in the normal population with the effect in a population receiving the agent.